全文获取类型
收费全文 | 311篇 |
免费 | 27篇 |
出版年
2024年 | 1篇 |
2022年 | 2篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 11篇 |
2017年 | 6篇 |
2016年 | 16篇 |
2015年 | 14篇 |
2014年 | 10篇 |
2013年 | 20篇 |
2012年 | 31篇 |
2011年 | 21篇 |
2010年 | 19篇 |
2009年 | 7篇 |
2008年 | 18篇 |
2007年 | 25篇 |
2006年 | 17篇 |
2005年 | 14篇 |
2004年 | 26篇 |
2003年 | 12篇 |
2002年 | 15篇 |
2001年 | 9篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 2篇 |
排序方式: 共有338条查询结果,搜索用时 843 毫秒
91.
Technikova-Dobrova Z Damiano F Tredici SM Vigliotta G di Summa R Palese L Abbrescia A Labonia N Gnoni GV Alifano P 《Applied microbiology and biotechnology》2004,65(6):671-677
Actinomadura sp. ATCC 39727 produces the glycopeptide antibiotic A40926, structurally similar to teicoplanin, with significant activity against Neisseria gonorrhoeae and precursor of the semi-synthetic antibiotic dalbavancin. In this study the production of A40926 by Actinomadura under a variety of growth conditions was investigated. The use of chemically defined mineral media allowed us to analyze the influence of carbon and nitrogen sources, phosphate, ammonium and calcium on the growth and the antibiotic productivity of Actinomadura. We confirm recent data [Gunnarsson et al. (2003) J Ind Microbiol Biotechnol 30:150–156] that low initial concentrations of phosphate and ammonium are beneficial for growth and A40926 production, and we provide new evidence that the production of A40926 is depressed by calcium, but promoted when l-glutamine or l-asparagine are used as nitrogen sources instead of ammonium salts. 相似文献
92.
1,2,3,4-Tetrahydroquinoline-containing alphaVbeta3 integrin antagonists with enhanced oral bioavailability 总被引:1,自引:0,他引:1
Ghosh S Santulli RJ Kinney WA Decorte BL Liu L Lewis JM Proost JC Leo GC Masucci J Hageman WE Thompson AS Chen I Kawahama R Tuman RW Galemmo RA Johnson DL Damiano BP Maryanoff BE 《Bioorganic & medicinal chemistry letters》2004,14(23):5937-5941
Reduction of the quinoline ring in an alpha(v)beta(3) antagonist yielded a 1,2,3,4-tetrahydro derivative as two diastereomers, the four isomers of which were separated by sequential chiral HPLC. Two isomers had significant alpha(V)beta(3) antagonist activity with improved oral bioavailability, relative to the corresponding quinoline derivative. 相似文献
93.
94.
Grano V Tasco G Casadio R Diano N Portaccio M Rossi S Bencivenga U Compiani M De Maio A Mita DG 《Biotechnology progress》2004,20(3):968-974
The inhibitory power of three different active Nylon membranes, separately loaded with three different protease inhibitors, was studied with the aim of reducing the increased elastase concentration occurring during hemodialysis or extracorporeal blood circulation in patients undergoing cardiopulmonary bypass. Chemical grafting was carried out to make the inert Nylon membrane suitable for the immobilization of the inhibitors. The behavior of immobilized alpha(1)-antitrypsin, bovine pancreatic trypsin inhibitor (BPTI), or elastatinal was separately studied. alpha(1)-Antitrypsin and BPTI were covalently immobilized by means of a diazotization process, whereas elastatinal was covalently attached via a condensation process mediated by glutaraldehyde. The inhibitory power of each membrane type was studied as a function of the amount of immobilized inhibitor and temperature. All active membranes have shown good inhibitory power. The most efficient membrane was that loaded with alpha(1)-antitrypsin, the less efficient that with BPTI. 相似文献
95.
Effect of Cu,Zn superoxide dismutase on cholesterol metabolism in human hepatocarcinoma (HepG2) cells 总被引:1,自引:0,他引:1
Mondola P Serù R Santillo M Damiano S Bifulco M Laezza C Formisano P Rotilio G Ciriolo MR 《Biochemical and biophysical research communications》2002,295(3):603-609
The microsomal enzyme 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase and the low density lipoprotein (LDL) receptor pathway carry out a key role on cholesterol homeostasis in eucaryotic cells. The HMG-CoA reductase is sensitive to oxidative inactivation and to phosphorylation by many kinases that are able to inactivate the protein and increase its susceptibility to proteolysis. We previously demonstrated that a calf thymus Cu,Zn SOD affects cholesterol metabolism. This protein binds with rat hepatocyte cell membrane by a specific surface membrane receptor. The involvement of Cu,Zn SOD in cholesterol metabolism is confirmed further by the presence of this antioxidant enzyme in circulating serum lipoproteins. We studied the effect of native human Cu,Zn SOD, metal-free SOD (apo SOD), and SOD-inactivated with hydrogen peroxide on cholesterol metabolism in human hepatocarcinoma HepG2 cells. Results showed that all forms of SODs used, at the concentration of 150 ng/ml, are able to affect cholesterol metabolism decreasing both HMG-CoA reductase activity and its protein levels; this inhibitory effect is accompanied by reduced cholesterol synthesis measured as [14C]acetate incorporation into [14C]cholesterol and by an increased [125I]LDL binding to HepG2 cells. Furthermore, the inhibitory effect of Cu,Zn SOD on cholesterol synthesis was completely abolished when the cells were incubated with Cu,Zn SOD in the presence of bisindoilmaleimide (BDM), an inhibitor of protein kinase C (PKC); moreover, we demonstrated that Cu,Zn SOD as well as apo SOD was able to increase PKC activity. Overall, data demonstrate that Cu,Zn SOD affects cholesterol metabolism independently from its dismutase activity and its metal content and that the inhibitory action on cholesterol synthesis is mediated by an activation of protein kinase C. 相似文献
96.
Lawson EC Hoekstra WJ Addo MF Andrade-Gordon P Damiano BP Kauffman JA Mitchell JA Maryanoff BE 《Bioorganic & medicinal chemistry letters》2001,11(19):2619-2622
Conformationally constrained analogues of the GPIIb/IIIa antagonist elarofiban (RWJ-53308) have been synthesized and biologically evaluated. The 1,2,4-triazolo[3,4-a]pyridine scaffold provided potent antagonists with favorable pharmacodynamic and pharmacokinetic attributes in dogs. Compounds 12a and 13a exhibited enhancements in oral bioavailability, t(1/2), and ex vivo duration of action (inhibition of ADP-induced platelet aggregation) relative to elarofiban. 相似文献
97.
98.
Roberta Iacono Nadia Minopoli Maria Carmina Ferrara Antonietta Tarallo Carla Damiano Caterina Porto Sandra Strollo Vronique Roig-Zamboni Gianfranco Peluso Gerlind Sulzenbacher Beatrice Cobucci-Ponzano Giancarlo Parenti Marco Moracci 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):2068
Pompe disease is an inherited metabolic disorder due to the deficiency of the lysosomal acid α-glucosidase (GAA). The only approved treatment is enzyme replacement therapy with the recombinant enzyme (rhGAA). Further approaches like pharmacological chaperone therapy, based on the stabilising effect induced by small molecules on the target enzyme, could be a promising strategy. However, most known chaperones could be limited by their potential inhibitory effects on patient’s enzymes. Here we report on the discovery of novel chaperones for rhGAA, L- and D-carnitine, and the related compound acetyl-D-carnitine. These drugs stabilise the enzyme at pH and temperature without inhibiting the activity and acted synergistically with active-site directed pharmacological chaperones. Remarkably, they enhanced by 4-fold the acid α-glucosidase activity in fibroblasts from three Pompe patients with added rhGAA. This synergistic effect of L-carnitine and rhGAA has the potential to be translated into improved therapeutic efficacy of ERT in Pompe disease. 相似文献
99.
The effects of chemical modifications of the Na+-H+ antiport in Escherichia coli have been analyzed by studying the resulting variations of the energy-dependent, downhill Na+ efflux from membrane vesicles. The histidyl reagent diethylpyrocarbonate (EtO)2C2O3 prevents the activation of the Na+ efflux mechanism by delta microH+ or its components. Inactivation of the antiporter by (EtO)2C2O3 is completely reversed by hydroxylamine. The data suggest that histidine residues are involved in the molecular mechanism of the Na+-H+ antiport. In contrast, no conclusive evidence suggesting participation of carboxylic, tyrosine or sulfhydryl residues in the Na+-H+ exchange reaction has been obtained. 相似文献
100.